This Program Project includes 7 Projects and 4 Cores. 7R01 grants will be associated with the Program Project and will share the cores. The central theme is a basic science effort to understand pain mechanisms. The levels of the rat nervous system to be investigated include primary afferent nociceptors and neurons in the dorsal horn of the spinal cord. PROJECT 1 will examine mechanisms of acute visceral pain. PROJECT 2 is concerned with the role of specific serotonin receptors in the modulation of dorsal horn neurons, using an in vitro slice preparation and whole cell patch clamping. PROJECTS 3-6 will study neuropathic pain in rats, using a model developed by our group. PROJECT 3 will examine three different models of neuropathic pain to examine their suitability as models of sympathetically maintained pain, sympathetically independent pain and adrenergically maintained pain. PROJECT 4 will investigate the sprouting of sympathetic postganglionic axons into dorsal root ganglia following spinal verse ligation and the role of nerve growth factor. PROJECT 5 evaluates the possibility that Abeta fibers sprout into lamina II and end on nociceptive processing neurons, thus changing dorsal horn circuitry. PROJECT 6 investigates a possible role of peripheral glutamate receptors in neuropathic pain. PROJECT 7 is an investigation of mechanisms of central pain in rats with chronically hemisected spinal cords. The cores include an ADMINISTRATIVE CORE, a COMPUTER CORE, a HIGH PERFORMANCE LIQUID chromatography core, and an ELECTRONICS CORE. The research team will take a multidisciplinary and collaborative approach to the investigation of pain mechanisms. Electrophysiological, morphological, pharmacological, neurochemical, and behavioral techniques will be utilized by teams of investigators, who will include not only the project directors and their trainees and technical staff, but generally also one or more other project directors. The long-term goal of the Program Project and the affiliated R01 grants is to provide insights into pain mechanisms that will help improve therapy for pain states that are currently difficult to manage clinically.